Extracellular ʜ ᴄ ᴏ3̅ is sensed by mouse cerebral arteries: Regulation of tone by receptor protein tyrosine phosphatase γ. Issue 5 (May 2016)

• Record Type: Journal Article
• Authors: Boedtkjer, Ebbe; Hansen, Kristoffer B; Boedtkjer, Donna MB; Aalkjaer, Christian; Boron, Walter F
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 36:Issue 5(2016)
• Page Start: 965
• Page End: 980
• Publication Date: 2016-05
• Subjects: Vascular biology -- basic science -- calcium imaging -- confocal microscopy -- electrophysiology -- endothelium -- experimental -- pH -- physiology -- receptors -- smooth muscle; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1177/0271678X15610787
• Languages: English
• ISSNs: 0271-678X

Abstract

We investigate sensing and signaling mechanisms for H +, HCO 3 - and CO2 in basilar arteries using out-of-equilibrium solutions. Selectively varying pHo, [HCO 3 - ]o, or pCO2, we find: (a) lowering pHo attenuates vasoconstriction and vascular smooth muscle cell (VSMC) Ca 2+ -responses whereas raising pHo augments vasoconstriction independently of VSMC [Ca 2+ ]i, (b) lowering [HCO 3 - ]o increases arterial agonist-sensitivity of tone development without affecting VSMC [Ca 2+ ]i but c) no evidence that CO2 has direct net vasomotor effects. Receptor protein tyrosine phosphatase (RPTP)γ is transcribed in endothelial cells, and direct vasomotor effects ofHCO 3 o - are absent in arteries from RPTPγ-knockout mice. At pHo 7.4, selective changes in [HCO 3 - ]o or pCO2 have little effect on pHi . At pHo 7.1, decreased [HCO 3 - ]o or increased pCO2 causes intracellular acidification, which attenuates vasoconstriction. Under equilibrated conditions, anti-contractile effects of CO2 /HCO 3 - are endothelium-dependent and absent in arteries from RPTPγ-knockout mice. With CO2 /HCO 3 - present, contractile responses to agonist-stimulation are potentiated in arteries from RPTPγ-knockout compared to wild-type mice, and this difference is larger for respiratory than metabolic acidosis. In conclusion, decreased pHo and pHi inhibit vasoconstriction, whereas decreased [HCO 3 - ]o promotes vasoconstriction through RPTPγ-dependent changes in VSMC Ca 2+ -sensitivity.HCO 3 o - serves dual roles, providing substrate for pHi -regulating membrane transporters and modulating arterial responses to acid–base disturbances.